Efficient Preparation of Aldoximes from Arylaldehydes, Ethylenediamine and Oxone ® in Water

The one-pot reaction of aromatic aldehydes, ethylenediamine and Oxone (2 KHSO5 x KHSO4 x K2SO4) in pure water was found to unexpectedly afford aldoximes in excellent yields.


Introduction
Oximation has attracted intensive attention for several decades as an efficient method for characterization and purification of carbonyl compounds.Due to the nucleophilic character of oximes, they have been widely used for the preparation of a variety of nitrogen-containing compounds such as amides [1], hydroximinoyl chlorides [2], nitrones [3] and nitriles [4].Oximes were usually prepared by the reaction of carbonyl compounds and hydroxylamine hydrochloride with adjustment of pH using a basic aqueous medium.Recently, some new techniques such as microwave irradiation [5] and solventfree heating [6] were applied to this reaction.Oxidation of amines or hydroxylamines was another usual method for the synthesis of oximes [7].
On the other hand, the use of water as a reaction medium has attracted notable interest and offers a clean, economical and environmentally-safe protocol for many reactions [8].In fact, more and more reactions have been reported to proceed smoothly and efficiently in water.In continuation of our interest in organic reactions in water [9], herein we report the unexpected formation of aldoximes from the one-pot reaction of aromatic aldehydes and ethylenediamine with Oxone ® in water.

Results and Discussion
Fujioka's, Konwar's and Sayama's groups have reported the reactions of aldehydes and ethylenediamine with oxidation by N-bromo(chloro)succinimide (NXS) [10], I 2 /KI/K 2 CO 3 /H 2 O system [11] or pyridinium hydrobromide perbromide (PHPB) [12].These reactions afforded dihydroimidazole-type products.Oxone ® has been widely used in organic reactions in recent years as an efficient and clean oxidant [13].When we employed Oxone ® as the oxidant for the reactions of aromatic aldehydes 1a-j and ethylenediamine (2) in pure water, to our surprise, no dihydroimidazoles were observed, and instead, aldoximes 3a-j were produced in excellent yields (Scheme 1).

Scheme 1.
1a-j 2 3a-j The procedure involves addition of ethylenediamine to an aqueous mixture of aldehyde and Oxone ® in water, followed by vigorous stirring in an oil bath to afford the aldoximes.The reaction was affected prominently by the quantity of Oxone ® employed and the optimum amount of this reagent was found to be one equivalent.If 1.5 equivalents or more of Oxone ® were used, the aromatic aldehydes could be partially oxidized to the corresponding benzoic acids.If 0.5 equivalents or less of Oxone ® were used, the conversions were relatively low.The ethylenediamine was used in slight excess.The reaction yields for the one-pot synthesis of aldoximes with the optimum molar ratio of 1, 2 and Oxone ® as 1:1.1:1 are listed in Table 1, along with the melting points of the products.a Isolated yields based on aldehydes.
From Table 1 it can be seen that all of the reactions of aldehydes 1a-j with 2 and Oxone ® gave very good yields of aldoximes 3a-j.All of the products except for 3g were known compounds and their structures were confirmed by comparison of their melting points, 1 H-and 13 C-NMR and IR spectra with reported data [5,[14][15][16][17][18].
The use of other amines replacing ethylenediamine was studied under the same conditions.Diamines such as 1,3-diaminopropane and 1,3-diaminohexane and aliphatic amines such as methylamine and butylamine afforded very low yields of the aldoximes, while p-tolylamine and hydrazine gave no aldoximes.These results demonstrated the advantage and special activity of ethylenediamine for the formation of aldoximes.
Other oxidants such as FeCl 3 , (NH 4 ) 2 Ce(NO 3 ) 6 , KMnO 4 , PhI(OAc) 2 and K 2 S 2 O 8 instead of Oxone ® have also been examined.None of these oxidants gave any aldoxime products, but rather generated the corresponding benzoic acids, thus clearly exhibiting the effectiveness of Oxone ® for producing aldoximes from aldehydes and ethylenediamine.Aliphatic aldehydes have also been used for these reactions, but unfortunately, they did not react with ethylenediamine and Oxone ® to afford aldoximes.
Additional control experiments were conducted to gain insight into the reaction mechanism.If the aqueous solution of 2 and Oxone ® was stirred at 80 o C for 3 h, and then an aldehyde was added and the resulting mixture stirred for another 3 h, no aldoxime was obtained.When Oxone ® was added after the aqueous solution of an aldehyde and 2 was stirred at 80 o C for 3 h, the desired aldoxime was successfully prepared in high yield.Consequently, the reaction mechanism is believed to proceed via the imine intermediate 4, which was then oxidized by Oxone ® to form the aldoxime product 3. Indeed, the reaction of the imine preformed from an aldehyde and 2 with Oxone ® for 3 h at 80 o C (Scheme 2) gave yields comparable to those obtained with the three-component one-pot process.Thus, for example, the oxidation of the imine 4a prepared from 1a and 2 with Oxone ® for 3 h at 80 o C afforded 3a in 89% yield, close to the 92% yield observed for the one-pot procedure (Table 1, entry 1).In contrast, the Oxone ® oxidation of the imines formed from 1a and 1,3-diaminopropane, 1,3-diaminohexane, methylamine or butylamine gave only small amounts of 3a, in contrast with the threecomponent one-pot process.These results again demonstrated the unique property of ethylenediamine for the generation of aldoximes.Scheme 2.

Conclusions
In summary, we have discovered a novel reaction of aromatic aldehydes, ethylenediamine and Oxone ® in pure water that provides a new route for the preparation of the corresponding aldoximes.Using this protocol, aldoximes were obtained with excellent yields.

Experimental
General 1 H-NMR and 13 C-NMR spectra were recorded at 300 MHz and 75 MHz respectively on a Bruker Avance-300 spectrometer using CDCl 3 as solvent.Chemical shifts (δ) are given in ppm relative to TMS as an internal standard and coupling constants (J) in Hz.IR spectra were taken on a Bruker Vector-22 spectrometer in KBr pellets and are reported in cm -1 .Melting points were determined on a XT-4 apparatus and are uncorrected.